Abstract

BACKGROUND The aim of this review is to investigate current uses of fibrinogen as a tool to reduce operative and postoperative blood loss in different surgical fields especially orthopedic spine surgery. This is a systematic review. METHODS MEDLINE (via Ovid 1946 to June 1, 2020) and Embase (via Ovid 1947 to June 1, 2020) were searched using the keywords "fibrinogen", "surgery", and "spine" for relevant studies. The search strategy used text words and relevant indexing to identify articles discussing the use of fibrinogen to control surgical blood loss. RESULTS The original literature search yielded 407 articles from which 68 duplications were removed. Three hundred thirty-nine abstracts and titles were screened. Results were separated by surgical specialties. CONCLUSIONS Multiple studies have looked at the role of fibrinogen for acute bleeding in the operative setting. The current evidence regarding the use of fibrinogen concentrate in spine surgery is promising but limited, even though this is a field with the potential for severe hemorrhage. Further trials are required to understand the utility of fibrinogen concentrate as a first-line therapy in spine surgery and to understand the importance of target fibrinogen levels and subsequent dosing and administration to allow recommendations to be made in this field.

Abstract

Anticoagulant therapy poses a significant risk for patients undergoing emergency neurosurgery procedures, necessitating reversal with prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). Data on PCC efficacy lack consistency in this setting. This systematic review and metaanalysis aimed to evaluate efficacy and safety of PCC for anticoagulation reversal in the context of urgent neurosurgery. Articles from PubMed, Embase, and Cochrane databases were screened according to the PRISMA checklist. Adult patients receiving anticoagulation reversal with PCC for emergency neurosurgical procedures were included. When available, patients who received FFP were included as a comparison group. Pooled estimates of observational studies were calculated for efficacy and safety outcomes via random-effects modeling. Initial search returned 4505 articles, of which 15 studies met the inclusion criteria. Anticoagulants used included warfarin (83%), rivaroxaban (6.8%), phenprocoumon (6.1%), apixaban (2.2%), and dabigatran (1.5%). The mean International Normalized Ratio (INR) prePCC administration ranged from 2.3 to 11.7, while postPCC administration from 1.1 to 1.4. All-cause mortality at 30 days was 27% (95%CI 21, 34%; I(2) = 44.6%; p-heterogeneity = 0.03) and incidence of thromboembolic events was 6.00% among patients treated with PCC (95%CI 4.00, 10.0%; I(2) = 0%; p-heterogeneity = 0.83). Results comparing PCC and FFP demonstrated no statistically significant differences in INR reversal, mortality, or incidence of thromboembolic events. This metaanalysis demonstrated adequate safety and efficacy for PCC in the reversal of anticoagulation for urgent neurosurgical procedures. There was no significant difference between PCC and FFP, though further trials would be useful in demonstrating the safety and efficacy of PCC in this setting.

Abstract

Bleeding and blood transfusion are common after scoliosis surgery. Fibrinogen is essential for blood clot formation and depletes quickly during haemorrhage. We randomly allocated 102 children 12-18 years old having surgery for idiopathic scoliosis, 51 to intra-operative fibrinogen concentrate 30 mg.kg(-1) (maximum 2 g) and 51 to saline placebo. Fibrinogen reduced peri-operative blood loss by a median (95%CI) volume of 155 (5-320) ml, from a median (IQR [range]) of 1035 (818-1420 [400-3030]) ml to 885 (755-1155 [270-2645]) ml, p = 0.04. Seven and four children received allogeneic red blood cell transfusion after fibrinogen and placebo, respectively, p = 0.34. There were no side-effects.

Abstract

BACKGROUND Surgical craniosynostosis repair in children is associated with massive blood loss and significant transfusion of blood products. Fibrinogen concentrate is claimed to be useful in reducing blood loss and transfusion requirements. OBJECTIVE We investigated whether prophylactic administration of fibrinogen concentrate will reduce blood loss and transfusion requirements during paediatric craniofacial surgery. DESIGN Randomised, placebo-controlled, double-blind clinical trial. SETTING University medical centre. PATIENTS A total of 114 infants and children up to 25 months of age (median age 10 months). INTERVENTION Surgical craniosynostosis repair by calvarial remodelling was performed in each patient. Patients were randomised to receive prophylactic fibrinogen concentrate (Haemocomplettan P) at a mean dose of 79 mg kg body weight or placebo. MAIN OUTCOME MEASURES Primary outcome was the volume of transfused blood products. Secondary outcomes were peri-operative blood loss, duration of surgery, length of stay in the paediatric ICU, length of hospital stay, postoperative complications and adverse effects of fibrinogen concentrate infusion. RESULTS No significant differences (P < 0.05) were found in the volume of transfused blood products (median 29 ml kg body weight vs. 29 ml kg body weight), intra-operative estimated blood loss (45 vs. 46 ml kg), calculated blood loss (57 vs. 53 ml kg), or postoperative blood loss (24 vs. 24 ml kg) between the intervention and placebo groups. In addition, duration of surgery, length of stay in the paediatric ICU, hospital stay and complications were not significantly different between the two groups. CONCLUSION During surgical craniosynostosis repair in young children, prophylactic administration of high-dose fibrinogen concentrate did not reduce the amount of transfused blood products or decrease peri-operative blood loss. TRIAL REGISTRATION National Trial Register (NTR2975) and EudraCT (2011-002287-24).

Abstract

Background: Spinal surgeries often have a high risk of hemorrhage during and after surgery, thus most patients require blood transfusions and blood products. Fibrinogen is used in different forms to control hemorrhage. Objectives: The present study aimed to evaluate the outcomes of prophylactic fibrinogen administration in reducing hemorrhage after lumbar surgery. Methods: This was a randomized clinical trial conducted on 30 patients undergoing lumbar surgery. The levels of fibrinogen, as well as hemoglobin (HB), hematocrit (HCT), prothrombin time (PT), partial thromboplastin time (PTT), and INR, were assessed preoperatively as the baseline values. The patients were divided into two groups: intervention (N = 15) and control (N = 15) groups. The intervention group received 1 g fibrinogen dissolved in 50 cc distilled water with surgical incision and the control group received 50 cc distilled water with the surgical incision. At the end of the operation, the volume of hemorrhage transfused blood products (fresh frozen plasma, packed cell, and platelet) was measured. In addition, at 0, 6, and 24 hours after the end of surgery and transfer to recovery, serum levels of fibrinogen, HB, HCT, INR, PT, PTT, and hemovac drain volume were measured. Results: The hemorrhage during and after the operation in the control group was significantly higher than that of the intervention group (P < 0.05). There were no significant differences between hemoglobin and serum level of fibrinogen before and after surgery between the two groups. The postoperative hypotension showed no significant difference between the two groups. Conclusions: The findings showed the effectiveness of fibrinogen in reducing acute hemorrhage. Considering the adverse consequences of hemorrhage and coagulopathy in patients undergoing surgery, using fibrinogen as prophylaxis is recommended in surgeries with high risks of hemorrhage.

Abstract

BACKGROUND Cerebrospinal fluid (CSF) leakage associated with incomplete sealing of the dura mater is a major complication of intradural procedures. OBJECTIVE To compare the efficacy and safety of adjunctive TachoSil (Takeda Pharma A/S, Roskilde, Denmark) with current practice for the prevention of postoperative CSF leaks in patients undergoing elective skull base surgery involving dura mater closure. METHODS Patients were intraoperatively randomized to TachoSil or current practice immediately before primary dura closure by suturing +/- duraplasty. Choice of adjunctive treatment in the current practice group was at the surgeon's discretion. Primary efficacy endpoint was occurrence of clinically evident verified postoperative CSF leak or clinically evident pseudomeningocele within 7 weeks after surgery or treatment failure (third application of trial treatment or use of other treatment). RESULTS A total of 726 patients were randomized to TachoSil (n = 361) or current practice (n = 365). More current practice patients had sutures plus duraplasty for primary dura closure compared with TachoSil (49.6% vs 35.7%) and fewer had sutures only (45.5% vs 63.2%). The primary endpoint of estimated leak rate favored TachoSil with events in 25 (6.9%) patients vs 30 (8.2%) current practice patients; however, this was not statistically significant (odds ratio: 0.82; 95% confidence interval: 0.47, 1.43; P = .485). Both treatments were well tolerated with similar frequency of adverse events. CONCLUSION Very low rates of postoperative CSF leaks can be achieved in patients undergoing skull base surgery of various indications. Although the study did not meet its primary endpoint, TachoSil appears to be safe and effective for the prevention of CSF leaks and associated complications.

Abstract

BACKGROUND Volume replacement therapy with colloid is still worth studying in major pediatric surgery with potential risk of bleeding. This study assessed the effects of 6% hydroxyethyl starch (HES) 130/0.4 and 5% Human Albumin (HA) on coagulation tested by thromboelastography (TEG) during elective intracranial tumor surgery in pediatric patients. METHODS In this randomized controlled trial, 60 patients undergoing intracranial tumor resection under general anesthesia were assigned to HES and HA groups (n = 30), and administered preloads of 20 mL . kg-1 HES 130/0.4 and 5% HA, respectively, prior to dura opening. Primary outcomes were perioperative thromboelastography findings, and hemodynamic and hematological parameters. Blood transfusion, perioperative fluid balance, intracranial pressure, mortality, intensive care unit stay, and hospital stay were also assessed. RESULTS TEG parameters did not differ after preloading compared to baseline values in either group, except for a decrease in maximum amplitude immediately after infusion (HES group, 57.6 +/- 6.0 mm vs. 50.9 +/- 9.2 mm; HA group, 60.1 +/- 7.9 mm vs. 56.6 +/- 7.1 mm; p < 0.01), which was restored to preoperative levels 1 h after fluid infusion. Total perioperative fluid balance, blood loss or transfusion, intracranial pressure, and hematological and hemodynamic variables were similar between both groups (p > 0.05). Mortality, length of hospital stay, and clinical complications were similar between both groups. CONCLUSION These findings suggest that HES and HA might have no significant differences regarding coagulation as assessed by TEG during pediatric intracranial tumor surgery with 20 ml/kg volume pre-loading, which can maintain stable hemodynamics and may represent a new avenue for volume therapy during brain tumor resection in pediatrics. TRIAL REGISTRATION ChiCTR-IPR- 16009333 , retrospectively registered October 8, 2016.

Abstract

BACKGROUND Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. METHODS A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. RESULTS A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. CONCLUSIONS A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.

Abstract

BACKGROUND Hypofibrinogenaemia is one of the main reasons for development of perioperative coagulopathy during major paediatric surgery. The aim of this study was to assess whether prophylactic maintenance of higher fibrinogen concentrations through administration of fibrinogen concentrate would decrease the volume of transfused red blood cell (RBCs). METHODS In this prospective, randomised, clinical trial, patients aged 6 months to 17 yr undergoing craniosynostosis and scoliosis surgery received fibrinogen concentrate (30 mg kg(-1)) at two predefined intraoperative fibrinogen concentrations [ROTEM() FIBTEM maximum clot firmness (MCF) of <8 mm (conventional) or <13 mm (early substitution)]. Total volume of transfused RBCs was recorded over 24 h after start of surgery. RESULTS Thirty children who underwent craniosynostosis surgery and 19 children who underwent scoliosis surgery were treated per protocol. During craniosynostosis surgery, children in the early substitution group received significantly less RBCs (median, 28 ml kg(-1); IQR, 21 to 50 ml kg(-1)) compared with the conventional fibrinogen trigger of <8 mm (median, 56 ml kg(-1); IQR, 28 to 62 ml kg(-1)) (P=0.03). Calculated blood loss as per cent of estimated total blood volume decreased from a median of 160% (IQR, 110-190%) to a median of 90% (IQR, 78-110%) (P=0.017). No significant changes were observed in the scoliosis surgery population. No bleeding events requiring surgical intervention, postoperative transfusions of RBCs, or treatment-related adverse events were observed. CONCLUSIONS Intraoperative administration of fibrinogen concentrate using a FIBTEM MCF trigger level of <13 mm can be successfully used to significantly decrease bleeding, and transfusion requirements in the setting of craniosynostosis surgery, but not scoliosis. CLINICAL TRIAL REGISTRY NUMBER ClinicalTrials.gov NCT01487837.Copyright © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Abstract

BACKGROUND Obtaining intra-operative watertight closure of the dura is considered important in reducing post-operative cerebrospinal fluid (CSF) leak. The purpose of this study was to evaluate a fibrin sealant as an adjunct to sutured dural repair to obtain intra-operative watertight closure in cranial neurosurgery. METHODS This randomized, controlled multicenter study compared a fibrin sealant (EVICEL Fibrin Sealant [Human]) to sutured dural closure (Control). Subjects underwent supratentorial or posterior fossa procedures. Following primary dural repair by sutures, the closure was evaluated for intra-operative CSF leak by moderately increasing the intracranial pressure. If present, subjects were randomized to EVICEL or additional sutures (2:1 ratio), stratified by surgical approach. Following treatment, subjects were successful if no CSF leaks were present during provocative challenge. Safety was assessed to 30 days post-surgery, including incidence of CSF leakage. RESULTS One hundred and thirty-nine subjects were randomized: 89 to EVICEL and 50 to Control. Intra-operative watertight closure was achieved in 92.1% EVICEL-treated subjects versus 38.0% controls; a treatment difference of 54.1% (p < 0.001). The treatment differences in the supratentorial and posterior fossa strata were 49.1% and 75.7%, respectively (p < 0.001). The incidence of adverse events was similar between treatment groups. No deaths or unexpected serious adverse drug reactions were reported. CSF leakage within 30 days post-operatively was 2.2% and 2.0% in EVICEL and control groups, respectively. In addition, 2 cases of CSF rhinorrhoea were observed in the EVICEL group. Although not associated with the suture line where EVICEL was applied, when combined with the other CSF leaks, the observed leak rate in the EVICEL group was 4.5%. CONCLUSIONS These results indicate that EVICEL is effective as an adjunct to dural sutures to provide watertight closure of the dura mater in cranial surgery. The study confirmed the safety profile of EVICEL.